T Cell Exclusion Mechanisms in B Cell Lymphomas
Discover how ATR-dependent determinants exclude T cells from germinal center dark zones in aggressive B cell lymphomas, shedding light on lymphoma biology and potential therapeutic targets.
Executive Brief
- The News: ATR-dependent determinants exclude T cells from germinal center dark zone.
- Clinical Win: ATR inhibition may improve T cell access to aggressive B cell lymphomas.
- Target Specialty: Hematopathology and Oncology for B cell lymphoma patients.
Key Data at a Glance
Category: Medical Research
Field of Study: Cell biology, Immunology, Oncology
Disease: Aggressive B cell lymphomas
Key Determinant: ATR-dependent determinants
Location of T cell Exclusion: Germinal center dark zone
Research Article ID: 10.1172/JCI187371
T Cell Exclusion Mechanisms in B Cell Lymphomas
Research ArticleCell biologyImmunologyOncology Open Access | 10.1172/JCI187371
Aggressive B cell lymphomas retain ATR-dependent determinants of T cell exclusion from the germinal center dark zone
Valeria Cancila,1 Giorgio Bertolazzi,2 Allison S.Y. Chan,3 Giovanni Medico,1,4 Giulia Bastianello,5 Gaia Morello,1 Daniel Paysan,6,7 Clemence Lai,3 Liang Hong,3 Girija Shenoy,3 Patrick W. Jaynes,3 Giovanna Schiavoni,8 Fabrizio Mattei,8 Silvia Piconese,9,10,11 Maria V. Revuelta,12 Francesco Noto,8 Luca Businaro,13 Adele De Ninno,13 Ilenia Cammarata,14 Fabio Pagni,15 Saradha Venkatachalapathy,6,7 Sabina Sangaletti,16 Arianna Di Napoli,17 Giada Cicio,18 Davide Vacca,1 Silvia Lonardi,19 Luisa Lorenzi,19 Andrés J.M. Ferreri,20,21 Beatrice Belmonte,1 Min Liu,3,22,23 Manikandan Lakshmanan,24 Michelle S.N. Ong,24 Biyan Zhang,25 Tingyi See,25 Kong-Peng Lam,25,26,27 Gabriele Varano,28 Mario P. Colombo,16 Silvio Bicciato,29 Giorgio Inghirami,4 Leandro Cerchietti,12 Maurilio Ponzoni,21,30 Roberta Zappasodi,31 Evelyn Metzger,32 Joseph Beechem,32 Fabio Facchetti,19 Marco Foiani,5 Stefano Casola,28,33 Anand D. Jeyasekharan,3,34,35,36 and Claudio Tripodo1,18,37
1Tumor Immunology Unit, Department of Health Sciences, University of Palermo, Palermo, Italy.
2Department of Medicine and Surgery, Kore University of Enna, Enna, Italy.
3Cancer Science Institute of Singapore, National University of Singapore, Singapore.
4Division of Hematopathology, Department of Pathology and Laboratory Medicine, Weill Cornell Medicine and NewYork-Presbyterian Hospital, New York, New York, USA.
5Genome Integrity Lab, IFOM ETS–The Italian Association for Cancer Research (AIRC) Institute of Molecular Oncology, Milan, Italy.
6Laboratory for Nanoscale Biology, Paul Scherrer Institute, Villigen, Switzerland.
7Department of Health Sciences and Technology, ETH Zürich, Zürich, Switzerland.
8Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
9Department of Internal Clinical Sciences, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy.
10Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Fondazione Santa Lucia, Unità di Neuroimmunologia, Rome, Italy.
11Laboratory affiliated to Istituto Pasteur Italia–Fondazione Cenci Bolognetti, Rome, Italy.
12Division of Hematology and Oncology, Medicine Department, Weill Cornell Medicine and NewYork-Presbyterian Hospital, New York, New York, USA.
13Institute for Photonics and Nanotechnologies, Italian National Research Council, Rome, Italy.
14Department of Translational and Precision Medicine, Sapienza University of Rome, Neuroimmunology Unit, IRCCS Fondazione Santa Lucia, Rome, Italy.
15Department of Medicine and Surgery, Pathology, IRCCS Fondazione San Gerardo dei Tintori, University of Milano–Bicocca, Milan, Italy.
16Molecular Immunology Unit, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
17Pathology Unit, Department of Clinical and Molecular Medicine, Sant’Andrea University Hospital, Sapienza University of Rome, Rome, Italy.
Clinical Perspective — Dr. Meera Pillai, Oncology
Workflow: As I assess patients with aggressive B cell lymphomas, I'm now considering the role of ATR-dependent determinants in T cell exclusion from the germinal center dark zone. The involvement of specific cellular mechanisms, such as those related to the germinal center, means I need to adjust my diagnostic approach. This adjustment involves considering the interactions between T cells and the tumor microenvironment.
Economics: The article doesn't address cost directly, but understanding the molecular mechanisms underlying T cell exclusion could lead to more targeted and potentially cost-effective treatments for aggressive B cell lymphomas. By identifying specific determinants like ATR, we may be able to develop therapies that improve patient outcomes without increasing healthcare costs. This could involve the use of existing drugs or the development of new ones that target these mechanisms.
Patient Outcomes: Patients with aggressive B cell lymphomas may benefit from a better understanding of the ATR-dependent determinants of T cell exclusion. By elucidating these mechanisms, we may be able to develop treatments that improve the efficacy of immunotherapies, such as those targeting the tumor microenvironment. For instance, therapies that enhance T cell infiltration into the germinal center dark zone could lead to improved patient outcomes, although specific outcome data is not provided in the article.
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